1. Field of the Invention
This invention relates to an automatic immunoassay analyzer. More particularly, the present invention relates to an immunoassay analyzer capable of measuring automatically and continuously at least one measurement (clinical testing) analyte for each of a plurality of specimens (the specimens as the objects of measurement) and more in particular, to a multiple immunoassay analyzer having a random access function which can freely select the random measurement analytes for each specimen.
2. Description of the Related Art
Various immunological clinical testing methods have been developed in the past. An example of such methods is described in "KOUSO MENEKI SOKUTEIHOU" (3rd edition) published by Igaku Shoin and "PRACTICE and THEORY of ENZYME IMMUNOASSAY", P. Tijssen, ELSEIER, AMSTERDAM, NEW YORK, OXFORD, and various methods are selected in accordance with the specimens of measurement and with the objects of measurement. Recently, a heterogeneous system has gained a wide application for achieving a high sensitivity measurement.
A method of measuring the quantity of an antigen contained in specimens such as blood collected as a specimen from a patient will be explained on the basis of a one-step sandwich method by way of example. In accordance with this method, the specimen as the object of measurement is added into a reaction vessel into which an antibody coupled to an insoluble support (solid phase) such as the inner wall of a synthetic resin vessel or particles (hereinafter referred to as the "immobilized antibody") and an antibody labeled by a label material such as a radioactive material, a fluorescent material, an enzyme, or the like (hereinafter referred to as the "labeled antibody") are in advance packed (so called sandwich). In the reaction vessel, the antigen contained in the specimen causes the antigen-antibody reaction with the immobilized antibody and the labeled antibody to form an antigen-antibody composite member and at the same time, the labeled antibody couples with this antigen-antibody composite member, thereby forming a composite member wherein the three components, that is, the immobilized - antigen - labeled antibody, are sandwiched.
In this manner the labeled antibody is coupled with the solid phase with the antigen in the specimen being the medium.
Next, the excessive labeled antibody which does not couple with the antigen added into the reaction vessel and the antibody components which do not participate in the immunological reaction other than the label coupled with this solid phase are subjected to isolation (hereinafter referred to as "B/F isolation"). Finally, the label quantity proportional to the antigen quantity coupled with the solid phase is measured quantitatively by physical or chemical means utilizing the properties of the label in order to determine the antigen concentration in the specimen.
In contrast, a two-step sandwich method carries out the first reaction by adding the specimen to the reaction vessel into which only the immobilized antibody is in advance charged, and then adds the labeled antibody to cause the second reaction.
In other words, the specimen is first added to the reaction vessel into which the immobilized antibody (or a reagent containing the same) is in advance charged. Thus, a specific antigen in the specimen causes the antigen - antibody reaction with the immobilized antibody and is coupled and fixed to the solid phase. The unreacted components which do not cause the antigen - antibody reaction are discharged outside the vessel through B/F isolation. Next, the labeled antibody is added to the reaction vessel so as to cause the antigen - antibody reaction. In this manner, the composite member of the immobilized antibody - antigen - labeled antibody is formed. The unreacted components and the reaction residue are subjected to B/F isolation and discharged outside the vessel.
After this operation, the amount of the composite coupled with the solid phase is measured by quantitative determination of the label material in the same way as in the one-step system described above so as to determine the antigen concentration in the specimen.
Besides these sandwich methods described above, a so-called "competitive method" is also known. This method causes the competitive reaction between the antigen in the specimen and the antigen labeled in advance by the label material (generally referred to as the "labeled antigen") at the same combined site of the immobilized antibody described above.
In accordance with this competitive method, the antigen in the specimen is reacted with the immobilized antibody and also the labeled antigen contained in the reagent is reacted with the immobilized antibody. Accordingly, the component (antigen) in the specimen as the object of measurement and the labeled antigen react competitively with the antigen - antibody reaction portion of the combined site of the immobilized antibody. As a result, the immunological composite members are formed respectively on the basis of the quantity ratio (concentration ratio) between the antigen component which is contained in the specimen and whose quantity is not known and the labeled antigen component whose quantity is in advance given. In this manner the antigen quantity in the specimen can be determined in accordance with the calculation proportional to the ratio described above by effecting the quantitative measurement of the quantity of the label material immobilized to the solid phase by utilizing the properties of the label material after B/F isolation of the unreacted materials and the reaction residue in the same way as the sandwich method.
As described above, the method of measuring quantitatively the quantity of the label material (which is sometimes referred to as a "marker") immobilized and coupled to the solid phase varies with the properties of the label material and according to the classification based on such an aspect, the immunoassay method is often referred to as FIA when a chemical fluorescent material is used for labeling, RIA when a radio-active material is used and EIA when an enzyme is used.
Detection and quantitative determination of trace amounts of living body materials and physiologically active substances by utilizing such immunological means are useful for diagnosis of various diseases and for the preparation of a remedial plan. For accurate diagnosis, the utilization of the analysis result of a plurality of different analytes is mostly effective and reagents and the like have conventionally been developed for measuring various living body components for the diagnosis of various diseases.
The immunological reaction measurement method used for the measurement of the physiologically active substances and the like utilizes in various manners the immunological reaction and the properties of the label material for measuring the antigen quantity either chemically or physically are also diversified. Accordingly, those apparatuses which have conventionally been developed for the measurement, particularly automated apparatuses having high industrial values, combine suitable methods and mechanisms in consideration of the measurement method of the immunological reaction and the problems peculiar to the properties of the label material, and a definite apparatus construction has been devised by further taking into consideration the feasibility of the apparatus when it is used in practice and the cost of the apparatus, equipment, operation, and the like. Recently, the development of a reagent kit for clinical diagnosis and apparatuses has drawn increasing attention and various attempts have also been made to design and construct such apparatuses.
However, most of the apparatuses that have conventionally been provided for these purposes do not sufficiently take into consideration the fact that the measurement operations are complicated because they need a large number of reagents such as peculiar immunological reagents, reaction reagents, reference specimens, and so forth, for the object material of measurement. For example, those apparatuses which have a large number of process steps which depend on the manual operation of a testing operator are not suitable for processing large quantities of samples.
Since the results of measurements are used directly as data for the diagnosis and foundation of the corresponding remedy, and since the remedial method varies with the measurements, an extremely high level of detection accuracy is required even though the apparatuses can deal with the measurement and quantitative determination of trace amounts of components, because the number of specimens requiring the testing operation described above which needs complicated and very careful attention and skill has tended to increase drastically in recent years but it is very difficult to maintain and secure a large number of skilled testing operators to meet such a large number of inspections. Accordingly, mistakes in inspection and accuracy management have become the critical problem.
For the reasons described above, the development of the apparatus which can eliminate as much as possible the errors and mistakes resulting from the individual difference of testing operators has been desired and the development of the automated apparatus which can rapidly process large quantities of specimens has also been desired.
As one of the automated immunological reaction measurement apparatuses for processing a large number of specimens in large quantities within a short period, an apparatus which processes batch-wise the measurement analyte common to a large number of specimens has been proposed in the past.
However, this batch processing system makes possible collective processing of only a specific analyte of measurement for a large number of specimens. Therefore, the number of measurement analytes is limited from the number of apparatuses, and the like. Though this system is effective when only a predetermined and constant analyte is tested, it is not suitable for the application wherein the measurement analytes are variously changed or selected. Furthermore, the system involves another problem that once the test for one analyte is started, the next inspection cannot be made till the end of the former. Moreover, the system is susceptible to the limitation of the operation because the specimens having the same measurement analyte must be gathered in order to improve efficiency of the collective processing of the single measurement analyte. For example, a large number of specimens gathered from various medical institutions and the like must be gathered and compiled once again in accordance with each measurement analyte, so that this compilation operation invites the drop of overall efficiency and induces the mistakes in the operation.
As an apparatus for solving such problems, a random access system apparatus having the following construction has been proposed (in Japanese Patent Laid-Open No. 148585/1987). Namely, a plurality of desired measurement analytes for each specimen are inputted and registered to an electronic control apparatus (a so-called "computer") and on the other hand, reaction vessels into each of which a reagent corresponding to each of these measurement analytes is in advance charged is selected. The reaction vessels are then placed in the sequence of the measurement analytes for each specimen on a tray (test plate) having m x n arranged openings, for example, and this tray is then fed into a measurement apparatus so as to carry out the measurement operation in accordance with the registered sequence described above.
This apparatus is advantageous because it can solve the problem of the conventional batch processing system in that the specimen aggregate must be formed in accordance with each measurement analyte.
However, the apparatus of the random access processing system requires the input and registration operation of the measurement analytes of each specimen by use of an input device such as a keyboard. In other words, though the apparatus can automate the operations after the start of measurement themselves, a great deal of burdensome are preparatory steps required manually before the start. Since the reaction vessels must be aligned on the tray in accordance with the registered sequence by use of the mechanized device, efficiency of the operation must yet be improved. Furthermore, the apparatus is likely to be expensive and the burden on equipment is great.